Heart disease, vascular disease and respiratory sleep disturbance are common and complex disorders with interactions among the cardiovascular, immune, neuroendocrine, sleep and circadian systems. Because inflammation in response to acute and chronic stress responsible for tissue damage associated with disease, recent efforts to understand mechanisms underlying these disorders have lead to studies that investigated inflammatory markers. These research efforts have revealed that high plasma levels of several novel inflammatory markers-cell adhesion molecules and pro-inflammatory cytokines-predict cardiovascular morbidity and mortality. High plasma levels of these markers are also reported to be associated with the severity of sleep apnea. A variety of stressors have been reported to initiate the inflammatory response, however, whether the stress of sleep deprivation also produces higher levels of these novel inflammatory markers is unknown. The current grant application takes an integrative physiological approach to understanding health consequences of sleep deprivation by forming new collaborations between experts in vascular physiology, neuronimmunophysiology, neuroendocrinology and sleep and circadian physiology. We are requesting funds to analyze existing biological specimens that were collected under controlled laboratory conditions from healthy women and men who underwent baseline sleep and wakefulness recording and 40 hours of total sleep deprivation. We propose to test the following specific hypothesis: 0 that acute total sleep deprivation will increase circulating levels of proinflammatory cell adhesion molecules; and ii) that acute total sleep deprivation will increase circulating levels of pro-inflammatory cytokines. We also propose to measure stress hormones to determine the relationship between changes in inflammatory cell adhesion molecules, cytokines and stress hormones during sleep deprivation and during baseline sleep. Because sleep loss is an independent risk factor for heart disease and chronic sleep loss is a consequence of sleep apnea, the results of the proposed study could have important implications for understanding the molecular mechanisms underlying these disorders and their association with sleep loss. This work could also have a significant impact on our understanding of the health consequences of sleep loss, which would have implications for public health and safety.